A novel ferroptosis-related gene signature for overall survival prediction and immune infiltration in patients with breast cancer

Abstract

Breast cancer is the most prevalent type of cancer among women worldwide. The heterogeneous nature of breast cancer poses a serious challenge for prognostic prediction and individualized therapies. Recently, ferroptosis, an iron-depen- dent form of programmed cell death, has been reported to serve a significant role in the regulation of the biological behavior of tumors. Several studies have revealed the prog- nostic significance of the ferroptosis-related gene (FRG) model; however, additional efforts are required to elucidate the details. Moreover, genes that modulate ferroptosis may be promising candidate bioindicators in cancer therapy. The present study systematically assessed the expression profiles of FRGs to reveal the relationship between FRGs and the prog- nostic features of patients with breast cancer based on data obtained from the Gene Expression Omnibus and Molecular Taxonomy of Breast Cancer International Consortium. Using a non-negative matrix factorization clustering method, patients with breast cancer were classified into two sub-groups (cluster 1 and cluster 2) based on the expression of FRGs. Furthermore, Cox regression, and least absolute shrinkage and selection operator methods were used to construct a risk score formula comprised of nine genes, which stratified patients with breast cancer into two risk groups. Patients belonging to the high-risk group exhibited significantly shorter overall survival (OS) time compared with patients in the low-risk group. The prognostic value of this signature was further verified in the training and validation cohorts. The results for univariate and multivariate Cox regression analyses indicated that risk score acted as an independent predictor for OS. Subsequently, a nomogram was constructed. Receiver operating characteristic analysis further confirmed that the resulting nomogram exhibited powerful discriminatory ability. Functional analysis revealed that the immune environment differed notably between the two groups and indicated an association between ferroptosis and breast cancer proliferation, migration and drug resistance. Taken together, the present study demonstrated that FRGs were significantly associated with breast cancer progression, and thus could be used as novel biomarkers for prognostic prediction and individualized treatment of patients with breast cancer.